Main content

Metabolism and degradation kinetics of selected veterinary medicines in manure

Introduction

The DFG research group "Veterinary drugs in soils: Basic research for risk analyses" explores the key processes that control both the fate and the ecotoxicological effects of selected veterinary drugs as model substances. Several subprojects have been established to investigate metabolism, binding mechanisms, ageing, effects on soil microbial structure, functioning and antimicrobial gene resistance. One of the main goals of this project is to elaborate a model for the risk assessment of veterinary drugs in the environment.

Most of the animal waste reaches soil as manure. As a result metabolized or non-metabolized animal drugs in liquid or solid animal waste may end up in the soil and subsequently are transported to surface and groundwater.

We study the fate and the metabolism of the sulfonamide sulfadiazine (SDZ) after administering the 14C-labelled veterinary drug to fattening pigs.

Approach

SDZ was applied on 4 consecutive days to pigs according to the recommended dosage of the producer. Daily sampling (ten days) of the manure started one day after the first application and each sample was analyzed at INFU. Primarily, the excretion kinetic of SDZ was determined and the metabolites were identified via 14C-detection and high selective and sensitive LC-MS/MS measurement. Trace level analysis of antibiotics and their metabolites in manure/soil is still a demanding task for the analytical chemist. Matrix effects could be overcome by advanced clean up procedures (two step solid phase extraction), spiking with 13C-labelled internal standard, and optimized LC-MS/MS conditions (Fig. 8).

Selected reaction monitoring (SRM) chromatograms of SDZ, internal reference standard and two major metabolites in manure

The same experiments were carried out at the same time with non-labelled SDZ in order to obtain manure for outdoor experiments.

Results

The main metabolites acetyl-sulfadiazine (AC-SDZ) and 4-hydroxy-sulfadiazine (4-OH-SDZ) and two hitherto unknown minor metabolites were found. The latter were identified as formylsulfadiazine (FOR-SDZ) and acetyl-4-hydroxysulfadiazine (AC-4-OH-SDZ) (Fig. 9).

Metabolic pathway of sulfadiazine after application of ^^14^^C-labelled drug to pigs

The excretion kinetics of sulfadiazine and its main metabolites are shown in Fig. 10 below.

Excretion kinetics of ^^14^^C-sulfadiazine and major metabolites

The results reveal the need for the determination of biotransformation products of veterinary medicines. In total only 44 % is excreted as parent compound.

The impact of veterinary medicines in manure sprayed to soil may therefore be underestimated if only the parent compound is considered.

In September 2005 spiked manure and manure after application of sulfadiazine to pigs was evenly distributed to the experimental field site of INFU. Sulfadiazine and its metabolites are rapidly sorbed or degraded in soil. The mechanism of this process is subject to further investigations.